Sarah Siska. C. A. Morales Felkin-1 Chem 206 Fe/kin 1968 energy difference(44H)between interactions of RM+0 and Rl +o determines product reactant-like"transition state reactant-like transition state assumption of torsional strain in partially formed or broken bonds first fully staggered acyclic model based on most stable ground-state contormauon substituents minimized around R: leads to Karabatsos model energy differences between major and minor inconsistency in aldehyde substrates conformations are <1 kcal/mol see DAE Chem 206 Lecture Notes(2000) 18-08 Felkin model olar effect: maximize separation between Nu-M LRL ∠RL incoming anionic nucleophile and electronegative substituent(Rs, RM, or RL Reduction of a-Methyl Ketones R RI= RL Me 16 anti-Felkin t-Bu 1.6 Rationalizations Features Rs 时→Nm=m most stable a)AH(imine N+R)AH(carbonyl 0+R) ground state b)imine geometry =complexed C=0 geometry substituents minimized around conformer (complexed C=OOFR) RL RL ketone R accounted for: leads to Karabatsos. G.J. J. Am. Chem. Soc. 1967. 89. 1367 Cherest, M. Felkin, H. Prudent, N. Tetrahedron Lett. 1968, 18, 2199R O M RS RL R O M RM RS RM O H M RM RL RS RS RL R O N H Z RM RL RS » O H RL RM RM RL Nu RM OH RL Nu RM OH RL O R RL Me RL RS RM R O M LiAlH4 RL RS RM R O M R RL Me OH R RL Me OH A B R Me Et i-Pr t-Bu RL RS RM Nu R OH Felkin: 1968 Chérest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 18, 2199 Felkin model • "reactant-like" transition state • assumption of torsional strain in partially formed or broken bonds: first fully staggered acyclic model • substituents minimized around R; leads to inconsistency in aldehyde substrates ➞ see DAE Chem 206 Lecture Notes (2000), 18-08 • polar effect: maximize separation between incoming anionic nucleophile and electronegative a-substituent (RS, RM, or RL) Nu: larger RL » better selectivity substituents minimized around ketone R 90° trajectory of nucleophile RL = Cy RL = Ph A / B 1.6 2.0 4.1 1.6 2.8 3.2 5.0 49 torsional strain accounted for; leads to fully staggered product + Features larger nucleophile » better selectivity Reduction of -Methyl Ketones Sarah Siska, C. A. Morales Felkin-1 Chem 206 Karabatsos model Nu: Nu: Karabatsos, G. J. J. Am. Chem. Soc. 1967, 89, 1367 • energy difference (DDH°) between interactions of RM ↔ O and RL ↔ O determines product ratio • reactant-like transition state • model based on most stable ground-state conformation • energy differences between major and minor conformations are <1 kcal/mol Nu-M + major (Felkin) minor (anti-Felkin) Rationalizations most stable ground state conformer a) DH°(imine N ↔ R) » DH°(carbonyl O ↔ R) b) imine geometry » complexed C=O geometry DH°(imine N ↔ R) » DH°(complexed C=O O ↔ R) Z = alkyl, OR, NR2 Nu: